The distribution of carbonic anhydrase isoenzymes I, II, and VI was studied in the human alimentary tract using specific antibodies to human isoenzymes in conjunction with the immunoperoxidase technique to elucidate the physiological role and possible functional interplay of carbonic anhydrases (CAs) in alimentary canal functions. From the isoenzymes studied, CA II was found to be the most widely distributed in the various epithelia throughout the alimentary canal. In addition to the acinar cells of the parotid and submandibular glands and the duodenal Brunner's glands, it was present in the mucosal epithelium of the oesophagus, stomach, duodenum, and colon. The epithelial cells of the hepatic bile ducts, gall bladder, and pancreatic ducts also contained CA II in abundance. In contrast, CA VI was present only in the serous acinar and ductal cells of the parotid and submandibular glands, and CA I in the mucosal epithelium of the colon and the A cells of the pancreatic Langerhans's islets. These results suggest that CA II as a widely distributed isoenzyme in the epithelia of the alimentary canal and CA VI as secreted into saliva, may form a mutually complementary system protecting oesophageal, gastric, and intestinal mucosa from acidity.